A multicentre randomised phase III trial comparing pembrolizumab vs single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial.

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Version: Author's accepted manuscript
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Serval ID
serval:BIB_0FC8052F2621
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A multicentre randomised phase III trial comparing pembrolizumab vs single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial.
Journal
Annals of oncology
Author(s)
Popat S., Curioni-Fontecedro A., Dafni U., Shah R., O'Brien M., Pope A., Fisher P., Spicer J., Roy A., Gilligan D., Gautschi O., Nadal E., Janthur W.D., Castro R.L., Campelo R.G., Rusakiewicz S., Letovanec I., Polydoropoulou V., Roschitzki-Voser H., Ruepp B., Gasca-Ruchti A., Peters S., Stahel R.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterized by limited treatment options and a poor prognosis. At relapse after platinum-based chemotherapy, single-agent chemotherapy is commonly used and single-arm trials of immune-checkpoint inhibitors have demonstrated encouraging activity.
PROMISE-meso is an open-label 1:1 randomised phase III trial investigating the efficacy of pembrolizumab (200mg/Q3W) vs institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy. Patients were performance status 0-1 and unselected for PD-L1 status. At progression, patients randomised to chemotherapy were allowed to crossover to pembrolizumab. The primary endpoint was progression-free survival (PFS), assessed by blinded independent central review (BICR). Secondary endpoints were overall survival (OS), investigator assessed (IA)-PFS, objective response rate (ORR), and safety. Efficacy by PD-L1 status was investigated in exploratory analyses.
Between September 2017 and August 2018, 144 patients were randomised, (pembrolizumab: 73; chemotherapy: 71). At data cut-off [20/02/2019, median follow-up of 11.8 months (IQR: 9.9-14.5)], 118 BICR-PFS events were observed. No difference in BICR-PFS was detected (HR=1.06, 95%CI:0.73-1.53; p=0.76), and median BICR-PFS (95% CI) for pembrolizumab was 2.5(2.1-4.2), compared with 3.4(2.2-4.3) months for chemotherapy. A difference in ORR for pembrolizumab was identified (22%, 95%CI:13%-33%), over chemotherapy (6%,95%CI:2%-14%; p=0.004). Forty-five patients (63%) assigned to chemotherapy, received pembrolizumab at progression. With follow-up to 21 August 2019 [17.5 months: 14.8-19.7)], no difference in OS was detected between groups (HR=1.12,95%CI:0.74-1.69; p=0.59), even after adjusting for cross-over. Pembrolizumab safety was consistent with previous observations. Exploratory efficacy analyses by PD-L1 status demonstrated no improvements in ORR/PFS/OS.
This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy. In biologically unselected patients, although associated with an improved ORR, pembrolizumab improves neither PFS nor OS over single-agent chemotherapy.
Keywords
Immune-checkpoint inhibition, Malignant pleural mesothelioma, Pembrolizumab, Randomized clinical trial
Pubmed
Create date
28/09/2020 8:09
Last modification date
28/10/2020 7:08
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